Blocking CCL3-mediated neutrophil recruitment into the brain alleviates immunopathology following severe enterovirus 71 infection

Wenxian Yang; Li Li; Guanlin Li; Xiuhui Li; Hongyan Liu; Xuelian Han; Yuan Wang; Yali Sun; Yuwei Wei; Bo Gao; Guangyu Zhao; Lei Sun; Min Li

doi:10.1016/j.isci.2024.111388

Blocking CCL3-mediated neutrophil recruitment into the brain alleviates immunopathology following severe enterovirus 71 infection

iScience. 2024 Nov 15;27(12):111388. doi: 10.1016/j.isci.2024.111388. eCollection 2024 Dec 20.

Authors

Wenxian Yang¹, Li Li², Guanlin Li^{3

4}, Xiuhui Li², Hongyan Liu⁵, Xuelian Han⁶, Yuan Wang⁶, Yali Sun⁶, Yuwei Wei⁶, Bo Gao⁷, Guangyu Zhao⁶, Lei Sun¹, Min Li⁶

Affiliations

¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
² You'an Hospital, Capital Medical University, Beijing, Fengtai 100069, China.
³ Associate Chief Technician, Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁴ Key Clinical Laboratory of Henan Province, Zhengzhou, China.
⁵ Shenyang Infectious Diseases Hospital, Shenyang, Liaoning Province, China.
⁶ State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China.
⁷ Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China.

Abstract

Inflammatory cells infiltration in the cerebrospinal fluid is a hallmark of severe enterovirus 71 (EV71) infection, but which type of immune cells are critical for severe EV71 infection remains unclear. Here, we observe that both neutrophils and macrophages are increased in the brains of patients and mice with severe EV71 infection, and the depletion of neutrophils but not macrophages results in a marked enhancement of survival of EV71-infected mice. Furthermore, CCR1/3 may play an important role in CCL3 facilitating the accumulation of neutrophils in the brains of patients. Inhibition of CCL3 by anti-CCL3 antibodies or selected miRNAs significantly reduces the neutrophils infiltration in brains and the mortality of EV71-infected mice. Collectively, CCL3-mediated neutrophils recruitment into the brain contributes to the severe immunopathology of EV71 infection, which provides a potential diagnostic and therapeutic target for EV71 infection.

Keywords: Clinical neuroscience; Immunology; Virology.